Heteroatomic nucleophiles catalytic reactions

Closely related to the ring-closing metathesis of enynes (Section 3.2.5.6), catalyzed by non-heteroatom-substituted carbene complexes, is the reaction of stoichiometric amounts of Fischer-type carbene complexes with enynes [266,308 -315] (for catalytic reactions, see [316]). In this reaction [2 + 2] cycloaddition of the carbene complex and the alkyne followed by [2 -t- 2] cycloreversion leads to the intermediate formation of a non-heteroatom-substituted, electrophilic carbene complex. This intermediate, unlike the corresponding nucleophilic carbene... 

The same transition metal systems which activate alkenes, alkadienes and alkynes to undergo nucleophilic attack by heteroatom nucleophiles also promote the reaction of carbon nucleophiles with these unsaturated compounds, and most of the chemistry in Scheme 1 in Section 3.1.2 of this volume is also applicable in these systems. However two additional problems which seriously limit the synthetic utility of these reactions are encountered with carbon nucleophiles. Most carbanions arc strong reducing agents, while many electrophilic metals such as palladium(II) are readily reduced. Thus, oxidative coupling of the carbanion, with concomitant reduction of the metal, is often encountered when carbon nucleophiles arc studied. In addition, catalytic cycles invariably require reoxidation of the metal used to activate the alkene [usually palladium(II)]. Since carbanions are more readily oxidized than are the metals used, catalysis of alkene, diene and alkyne alkylation has rarely been achieved. Thus, virtually all of the reactions discussed below require stoichiometric quantities of the transition metal, and are practical only when the ease of the transformation or the value of the product overcomes the inherent cost of using large amounts of often expensive transition metals. 

Two systems have been developed to the level of useful organic synthesis methodology spontaneous coordination of the alkene to Pd and the preparation of discrete Cp(CO)2Fe-alkene cationic complexes. With the Pd system, efficient catalytic processes have been developed for the addition of heteroatom nucleophiles, while the coupling with carbon nucleophiles is mainly relegated to stoichiometric reactions these two topics will be presented separately. In the iron series, the reactions involve stable intermediates and are invariably not amenable to catalysis. 

For example, (C5Me5)RuCl(cod) showed high catalytic activity for allylic substitution by amines (heteroatom nucleophiles that fail with Mo and W catalysts) under extremely mild reaction conditions (0 °C, for 1 h >99% yield). The reaction is also highly regioselective to give branched N-allylamines as a major product (Eq. 5.31) [29]. 

Wacker-type reactions are Pd(II)-catalyzed transformations involving heteroatom nucleophiles and alkenes or alkynes as electrophiles [108]. In most of these reactions, the Pd(ll) catalyst is converted to an inactive Pd(0) species in the final step of the process, and use of stoichiometric oxidants is required to effect catalytic turnover. For example, the synthesis of furan 113 from a-allyl-P-diketone 112 is achieved via treatment of the substrates with a catalytic amount of Pd(OAc)2 in the presence of a stoichiometric amount of C uC F [109]. This transformation proceeds via Pd(lt) activation of the alkene to afford 114,... 

Catalytic reactions of allylic electrophiles with carbon or heteroatom nucleophiles to form the products of formal S 2 or S 2 substitutions (Equation 20.1) are called "catalytic allylic substitution reactions." Tliese reactions have become classic processes catalyzed by transition metal complexes and are often conducted in an asymmetric fashion. The aUylic electrophile is typically an allylic chloride, acetate, carbonate, or other t)q e of ester derived from an allylic alcohol. The nucleophile is most commonly a so-called soft nucleophile, such as the anion of a p-dicarbonyl compound, or it is a heteroatom nucleophile, such as an amine or the anion of an imide. The reactions with carbon nucleophiles are often called allylic alkylations. 

Abstract Iron-catalyzed C-H bond activation followed by C-C bond formation has received much attention in recent years, motivated by the environmental and economical merits of iron, as well as the scientific challenge in controlling and understanding the reactivity of iron species. This review describes the utilization of iron as a catalyst for directed C-H bond activation, followed by C-C bond formation. Catalytic activation of C(sp )-H and C(sp -H) bonds, followed by oxidative reaction with nucleophiles, or reaction with electrophiles is described. Reactions of substrates possessing a directing group are mainly discussed, but other substrates are also presented. Carbon-heteroatom bmid formation is also briefly discussed. 

The direct, Pd(II)-catalyzed addition of heteroatom and stabilized carbon nucleophiles to alkenes is generally not a successful reaction. An exception is the addition of water, which gives carbonyl compounds and has been developed into an important indnstrial process, the Wacker process. This has been reviewed extensively.By contrast, the stoichiometric addition of nucleophiles such as amines is facile. - However, if alkenes could be converted catalytically into Tr-allylpalladium complexes, the problems with nucleophilic addition to alkenes could be circumvented and amines and other heteroatom nucleophiles could be employed. A range of alkenes have been converted into rr-allyl complexes in a stoichiometric fashion,t "t but catalytic reactions have proved more difficult. However, aUyl acetates and similar compounds readily exchange the acetate group for heteroatom nucleophiles in a Pd(0)-catalyzed reaction, which proceeds via 7T-allylpalladinm(ll) intermediates (Scheme 1). Since this reaction has been developed into a very important synthetic reaction, an efficient procedure for catalytic conversion of alkenes into aUyl acetates would have great synthetic potential. 

A number of intramolecular Pd-catalyzed 1,4-oxidations of conjugated dienes were developed.f In these reactions, two nucleophiles are added across the diene, one of which adds intramolecularly. So far, only heteroatom nucleophiles have been employed. In order to extend these intramolecular 1,4-oxidations to carbon nucleophiles, it was found that a vinylpalladium species can be obtained in situ from an alkyne via a chloropalladation. The approach is particularly attractive since it involves a Pd(II) chloride salt and could be compatible with the rest of the catalytic cycle. Reaction of dienyne with LiCl, and benzoquinone in the presence of palladium acetate as the catalyst, afforded the carbocyclization products. The reaction resulted in an overall stereoselective fltiri-addition of carbon and chlorine across the diene t B (Scheme 23). 

The acyl palladium intermediate may also be trapped by heteroatom nucleophiles (Schemes 4.17 and 4.18), such as alcohols and amines as part of the catalytic process, to give esters (Scheme 4.19) and amides (Scheme 4.20), respectively. Less commonly used nucleophiles include water, to give carboxylic acids, carboxylate salts, to give anhydrides, and ketones, via their enol form, to give enol esters. Metal carbonyl complexes may be used as both the source of CO and as the catalyst for the reaction (Scheme 4.21). ... 

Making acetals that contain A-atoms has been a fairly straightforward effort, following the advent of asymmetric phosphoric acid catalysis [9, 10]. Since the reports of Akiyama and Terada, asymmetric additions of nucleophiles to imines became a well-developed area of asymmetric Brpnsted acid catalysis [11, 12]. Consequently, heteroatom nucleophiles were shown to be viable nucleophiles and various N,N-, N,0-, and A,S -acetals could be prepared for the first time in a catalytic asymmetric fashion. These reactions are briefly summarized in the next section. 

Other Heteroatom Nucleophiles. Alcohols and carboxylic acids also add to metal-activated alkenes, and processes for the industrial conversion of ethylene to vinyl acetate and acetals are well established. However, these processes have not been extensively used with more cort5)lex alkenes. In contrast, a number of intramolecular versions of the processes have been developed, a few examples of which are given here. Allylphenols cyclize readily in the presence of palladium(II) to form benzofurans (eq 4). Catalytic amounts of palladium acetate can be used if the reaction is carried out under 1 atm of molecular oxygen with copper diacetate as cooxidant, or in the presence of tert-butyl hydroperoxide. If instead of palladium acetate a chiral jr-allylpalladium acetate complex is used, the cyclization proceeds to yield 2-vinyl-2,3-dihydrobenzofuran with up to 26% ee. ... 

Electron transfer from the alkene leads to a radical cation that can undergo coupling (Scheme la). The radical cation can also react with the nucleophilic heteroatom of a reagent to afford addition or substitution products (Scheme lb). Adducts can be likewise obtained by oxidation of the nucleophile to a radical that undergoes radical addition. Reactions between alkenes and nucleophiles can be realized too with chemical oxidants that are regenerated at the anode (mediators) (see Chapter 15). Finally, cycloadditions between alkenes can be initiated by a catalytic anodic electron transfer. These principal reaction modes are subsequently illustrated by selected conversions. 

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